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Nonhypoxic Pathway Mediates the Induction of Hypoxia-inducible Factor 1α in Vascular Smooth Muscle Cells

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Richard, Darren E., Berra, Edurne, Pouysségur, Jacques·2000·Journal of Biological Chemistry

Abstract

Hypoxia-inducible factor-1 (HIF-1) controls the expression of a number of genes such as vascular endothelial growth factor (VEGF) and Erythropoietin in low oxygen conditions (hypoxia). VEGF is strongly induced at both the mRNA and protein expression level by a number of hormones and growth factors in vascular smooth muscle cells (VSMC) independently of the oxygen environment. However, the role of HIF-1α in this induction has not been studied. We report here that HIF-1α protein levels are strongly increased by fetal calf serum in quiescent VSMC. More interestingly, Angiotensin II (Ang II), thrombin, platelet-derived growth factor, and other hormones can also increase HIF-1α in VSMC to levels that are substantially more elevated than the hypoxic treatment. HIF-1α induced by Ang II is located in the nucleus, binds to the hypoxic response element, and is transcriptionally active. The induction of HIF-1α by hormones is mediated through the production of reactive oxygen species (ROS), since it can be blocked by the ROS inhibitors, diphenyleneiodonium and catalase. Finally, strong induction of VEGF mRNA by Ang II can also be inhibited by these ROS inhibitors. These results implicate HIF-1α and HIF-1-dependent transcriptional activity in the induction of VEGF expression after agonist stimulation and define novel hypoxia-independent mechanisms that should play a major role in vascular remodeling.

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Metadata

Authors
Richard, D. E., Berra, E., & Pouysségur, J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-09
Volume
275
Issue
35
Pages
26765-26771
ISSN
0021-9258 (ISSN-L)
OpenAlex
W4254763216
Cited by
488
References
7
FWCI
11.72
Type
journal article
Language
en
Open access
hybrid
Licence

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CoChat. (2026). Citation check: Nonhypoxic Pathway Mediates the Induction of Hypoxia-inducible Factor 1α in Vascular Smooth Muscle Cells. https://app.cochat.ai/papers/10.1016/s0021-9258(19)61441-9
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Richard, D. E., Berra, E., & Pouysségur, J. (2000). Nonhypoxic Pathway Mediates the Induction of Hypoxia-inducible Factor 1α in Vascular Smooth Muscle Cells. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(19)61441-9

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